The long range goal of this portion of the PPG is to evaluate the pharmacodynamics of selective opioid peptide analogues on the cardiorespiratory and metabolic parameters which play a role in maintaining fetal viability, normal fetal growth and development, and a smooth transition to neonatal life. The specific aims for the initial 5 years of the project are focused to achieve 3 goals. They are: 1) To characterize the maternal and fetal hemodynamic and metabolic dose- response relationship for new opioid peptide analogues which are highly selective for the mu and delta receptor. The outcome parameters will include: maternal respiratory rate, uterine blood flow, and uterine vascular resistance as well as heart rate, blood pressure, blood pH, p)2, PC02, hemoglobin, protein, )2, glucose and lactate content in both mother and fetus; 2) to confirm the mu and/or delta receptor selectivity for the pharmacodynamic actions that are identified for each opioid peptide analogue using selective mu and delta antagonists; 3) to characterize the pharmacodynamic effects of a select group of these opioid peptide analogues on: utero-placental and fetal oxygen, glucose, and lactate utilization, placental perfusion balance, and flow distribution within the fetus. These data will provide definitive information in 3 areas. First, they will be used to test the second general hypothesis of the PPG: that delta selective opioid peptide analogues will have fewer adverse metabolic and hemodynamic effects on the mother and fetus than selective mu opioid peptide analogues. Second, they will provide in depth understanding of the physiological mechanisms which underlie the adverse affects of opioids on the feto-placental unit. Third, they will identify a set of synthetic opioid peptide analogues whose structure provide the appropriate receptor selectivity and pharmacodynamic action to recommend them as candidates for safe acute and chronic use in human pregnancy.